As part of our Q&A series on histamine, Dr Joneja was asked what the difference was between histamine intolerance and Mast Cell Activation Disorder (or Mastocytosis) and whether a low histamine diet could help.

Question:

Could you help me understand the difference between histamine intolerance and Mast Cell Activation Disorder/Syndrome?
The symptoms for both are about the same. My doctor think I have MCAD and I’m wondering if a low histamine diet would help me.

Dr Joneja says:

Thank you for this question, which, in answering, I hope to help other people with MCAD who have contacted me with similar queries.

The term mast cell activation disorder, or systemic mastocytosis, includes a number of different disorders with symptoms in various organ systems. The basis for the condition is a genetic mutation that results in the production of excessive numbers of mast cells.

Mast cells are white blood cells (leukocytes) that are located in tissues throughout the body, in contrast to other types of white blood cells such as basophils, neutrophils, monocytes and lymphocytes, that tend to circulate in blood. There are especially large numbers of mast cells in the skin, respiratory tract, digestive tract, urinary tract, around blood vessels and lymphatic vessels, around nerves, and in reproductive organs. Mast cells manufacture (synthesise) and store chemicals that are designed to protect the body from threat, such as infection, trauma, and other dangers and diseases, and to aid in the repair of tissues once the threat has been eradicated. They are also responsible for the allergic reaction, which in effect is a “protective” response to a foreign agent entering the body, albeit a misguided one. The protective chemicals, called inflammatory mediators, are stored within the mast cell in discrete granules (hence the name “granulocyte” for this type of white blood cell) in a matrix of proteoglycans (protein-sugar complexes) including heparin. Inflammatory mediators within the granules include histamine, chemotactic factors (chemicals that induce the movement of other granulocytes to the reaction site) and several enzymes including tryptase. One specific enzyme, phospholipase A2, acts on the cell membrane to release arachidonic acid (an omega-6 fatty acid) which in turn is metabolised to leukotrienes and prostaglandins, both of which have profound effects on smooth muscle. When the mast cell is activated, either in a protective immune response, an allergic reaction, or in response to other triggers, there is a change in energy at the cell surface, calcium enters the cell and the granules are released, expelling their contents into the surrounding tissues. The effect of these mediators on the tissues and organs in which they are located results in symptoms, typified by inflammation and allergy.

I have provided this rather complex explanation in order for you to appreciate that mast cells do not simply release histamine, but are responsible for releasing many reactive agents that induce symptoms in addition to those produced by histamine. When there is an excessive number of mast cells in any organ, a vastly increased quantity of inflammatory mediators is released whenever an event triggers degranulation (release of the granules). This results in the distressing symptoms typically experienced by people suffering from mast cell activation disorder.
The term “histamine intolerance”, in contrast, is usually reserved for a condition in which excess histamine is the only disorder. Typically a person experiences symptoms indistinguishable from allergy, but when tested, no evidence of allergy can be found. Frequently there is a deficiency in the enzyme systems that break down excess histamine, principally diamine oxidase (DAO). As a result of the deficiency, histamine builds up to a level that exceeds the person’s limit of tolerance (the level above which symptoms develop). The level of histamine can often be controlled by a histamine-restricted diet in which all histamine-containing and releasing foods are eliminated, resulting in a level that remains within normal limits, affording the patient relief of their symptoms – see here for more on this.

However, there are a number of disorders that result in the build-up of histamine in excess of the person’s limit of tolerance, separate and distinct from DAO deficiency. These include any condition that involves the release of histamine, such as infection, inflammation from a variety of causes, autoimmune diseases of various types, allergy, and of course, mast cell activation disorder. If a person has a DAO deficiency, in addition to these complaints, the situation is made even more acute. Because histamine is released in significant quantities, any event that triggers mast cell degranulation will lead to histamine build-up. If there is an excessive number of mast cells in the body, histamine will increase in proportion to the number of mast cells involved. In systemic mastocytosis and mast cell activation disorders, many of the symptoms experienced, but by no means all, will be caused by histamine excess. Therefore, a histamine-restricted diet will definitely reduce the amount of histamine in the body by limiting the amount of extrinsic (from outside the body) histamine contributing to the total. However, because the excess histamine is being released from mast cells within the body (intrinsic histamine), a histamine-restricted diet would be expected to improve a person’s symptoms, but not to eliminate them altogether. Furthermore, because inflammatory mediators in addition to histamine are released in mast cell degranulation, other symptoms for which histamine is not responsible, will not be affected.

So, to answer your question: a histamine-restricted diet will definitely help to improve the symptoms associated with histamine. However, because histamine is not the only culprit, symptoms caused by the other inflammatory mediators released from your excessive numbers of mast cells will continue to be a problem and may need to be controlled by appropriate medications.

If the cause of histamine intolerance or excess histamine is a mast cell disorder (like mast cell activation syndrome) and not DAO deficiency would a low histamine diet help to reduce symptoms? Or should people with mast cell disorders only stay away from foods that are histamine liberators like strawberries and egg white?

Dr Joneja says:

As I have discussed in previous articles, mast cell activation disorders involve large numbers of mast cells far in excess of “normal”. Each of the mast cells contains numerous granules that store inflammatory mediators, protective chemicals that under normal circumstances are released to defend the body from threats such as infection, trauma and numerous diseases. One of the first of the inflammatory mediators, released in large quantities, is histamine. However, there are several other important, powerful mediators in addition to histamine that are discharged from the granules at the same time or soon after histamine. Each of these have different effects on the body’s tissues and organs. So in mast cell activation disorders we see the consequences of the activities of an overabundance of mediators such as prostaglandins, leukotrienes, and various enzymes, in addition to histamine. A histamine-restricted diet will definitely reduce the effects of the excess histamine in mast cell activation disorders, but will have little effect in counter-acting the other mediators.

In diamine oxidase (DAO) deficiency, in contract, we see the effects of excess histamine that results from an inefficient system of clearing the body of histamine to maintain a normal level. Histamine builds up to beyond a person’s “limit of tolerance” (the level above which symptoms develop). No other mediators are involved (unless, of course, the person has a mast cell disorder in addition to DAO deficiency), so a histamine-restricted diet will usually allow the person to maintain a symptom-free status under normal circumstances.

Simply avoiding foods such as strawberries and egg whites will not have any noticeable effect on either histamine sensitivity as a result of DAO deficiency, or excess histamine released in mast cell activation disorders. In either situation it is necessary to avoid all histamine-associated foods (histamine-containing, and histamine-releasing foods and additives) to reduce the histamine level below a person’s limit of tolerance.

If you found this article interesting you can find a number of other articles on histamine intolerance both by Dr Joneja and others here, reports on histamine research here and a Q & A section on histamine with Dr Joneja here.

For many, many other articles on every type of food allergy and intolerance click here; for coeliac disease and other food related conditions, go here.

Dr Janice Joneja Ph.D., RD

Dr. Janice Joneja is a researcher, educator, author, and clinical counsellor with over thirty years of experience in the area of biochemical and immunological reactions involved in food allergy and intolerances. Dr. Joneja holds a Ph.D. in medical microbiology and immunology and is a registered dietitian (RD).

She has been a member of the faculty at several Canadian universities, starting her career as an Assistant Professor in the Department of Microbiology, Faculty of Science, and in the Faculty of Dentistry, at the University of British Columbia, Vancouver. Since 2001 Dr. Joneja has been a faculty member in the School of Biomedical and Molecular Sciences, at the University of Surrey, in England, teaching in the M.Sc. course in Nutritional Medicine. For 12 years she was head of the Allergy Nutrition Program at the Vancouver Hospital and Health Sciences Centre.

Dr. Joneja is the author of six books and a dietetic practice manual on food allergy, a textbook on Irritable Bowel Syndrome, and several distance education courses. Her most recent books include “The Health Professional’s Guide to Food Allergies and Intolerances”, “Dealing with Food Allergies”, and “Dealing with Food Allergies in Babies and Children”. Dr. Joneja’s work has been published in peer-reviewed scientific and medical journals, as well as in popular magazines. She is a respected lecturer at universities, colleges and hospitals internationally, and regularly appears on television and radio call-in shows as an expert in her field.

Dr. Joneja is President of Vickerstaff Health Services, Inc., a practice that provides counselling for people suffering from all aspects of adverse reactions to food, and resources for the professionals and care-givers who support them.